Abstract
BackgroundWe have recently reported that Origanum majorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Here, we extended our study by investigating the effect of O . majorana on the migration, invasion and tumor growth of these cells.ResultsWe demonstrate that non-cytotoxic concentrations of O . majorana significantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show that O . majorana induce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show that O . majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits transendothelial migration of MDA-MB-231 through TNF-α-activated HUVECs. Gelatin zymography assay shows that O . majorana suppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western blot results revealed that O . majorana decreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further investigation revealed that O . majorana suppresses the phosphorylation of IκB, downregulates the nuclear level of NFκB and reduces Nitric Oxide (NO) production in MDA-MB-231 cells. Most importantly, by using chick embryo tumor growth assay, we also show that O . majorana promotes inhibition of tumor growth and metastasis in vivo.ConclusionOur findings identify Origanum majorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis.
Highlights
Breast cancer is the leading cause of cancer-related deaths in women worldwide
Because cell migration plays a crucial role in tumour metastasis, we sought to investigate whether Origanum majorana ethanolic extract (OME) affects the migration behaviour of MDA-MB-231 cells, we first measured the migration ability of these cells by using wound-healing migration assay
We demonstrate for the first time that O. majorana, at noncytotoxic concentrations, possesses potent anti-metastatic activities against the highly invasive triple negative breast cancer cell line, MDA-MB-231
Summary
Breast cancer is the leading cause of cancer-related deaths in women worldwide. Approximately one-third of all women with breast cancer develops metastasis and dies as a result of the effects of the disease [1,2]. Induces the disassembly of cancer cells from the primary tumor, disseminating them to distant sites through blood vessels and lymphatics, and eventually leave the circulation to establish metastasis in distant organs [3,4]. A cell–cell adhesion molecule, plays a major role in the establishment and maintenance of normal tissue architecture It is expressed predominantly on the surface of normal epithelial cells. For cancer cells to become metastatic, they must decrease E-cadherin expression and break these cell-cell adhesions associated and induction of cell mobility triggering a transition from tumorigenic (epithelial) to migratory/ invasive (mesenchymal) phenotype ending in tumor metastasis. We have recently reported that Origanum majorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Conclusion: Our findings identify Origanum majorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis
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